Preliminary studies have shown that nerve fibers containing serotonin are within the rat pancreas. Previously, serotonergic fibers had been described only in the brain and in the intestinal wall. Cells of the endocrine islets of the pancreas have been shown to contain serotonin but only under unphysiological conditions. The ontogeny, distribution and pharmacology of the serotonergic nerves of the pancreas will be studied. The relationships of the nerve endings to the islet cells will be examined. These nerve fibers may have a role in the regulation of insulin, glucagon or somatostatin secretion. To examine this hypothesis, a specific serotonergic neurotoxin will be used to selectively ablate these fibers. The dynamics of islet cell secretion will then be measured using both in vivo and in vitro techniques. By these studies, we hope to gain a better understanding of the role of the serotonergic nerve fibers in the development and function of the endocrine pancreas.